Bacterial persistence is of major concern worldwide in the control of a number of bacterial infections. The carriers who are asymptomatic act as reservoirs of the bacteria. Knowledge of the host response, of the persistence process, and of the potential of biological mediators as diagnostic markers is essential towards development of prophylactic and treatment modalities for these diseases. Immune mechanisms related to recognition and elimination of the bacteria play pivotal roles in the control of bacterial infections. The majority of the studies on bacterial infections detail the immune mechanisms in the active phase of infection, and reports on the immune status in carriers are scanty. The present review describes the role of recognition molecules (TLRs) and the immune mediators (cytokines) in bacterial persistence. It appears that the TLR-mediated induction of cytokine profiles differs in active infection and bacterial persistence, with an active Th1 response being beneficial for the clearance of a high load of bacteria and at the same time conducive for the persistence of low bacterial load. Immunomodulation aiming at stimulation of the immune responses should be carried out with care as it could give rise to a carrier state in individuals with low load of the bacteria.